Errors in recombination

Structural abnormalities

This is known as recombination and is key to ensuring offspring have different genetic traits to their parents. However, if homologous chromosomes (chromosomes of the same pair) misalign or non-homologous chromosomes pair, a number of different structural chromosome abnormalities may result including chromosome deletions / duplications; translocations and chromosome inversions.

Deletions or Duplications

This refers to the loss (deletion) or gain (duplication) of genetic material. A deletion or duplication is called interstitial when it occurs in the middle of the chromosome and terminal when it occurs at the tip of the chromosome.

The phenotypic (clinical) effect of a deletion or duplication depends on the genes involved. Deletions are generally more likely to have a phenotypic effect than duplication. Large deletions are likely to be lethal.

One of the commonest microdeletion syndromes is Di George syndrome, involving deletion of a region of chromosome 22 called 22q11. Di George syndrome can cause a variety of problems, including heart abnormalities, defects of the palate, problems of immunity and calcium control. Children and adults often have a characteristic facial appearance.

With the advent of array testing, an increasing number of recurrent microdeletion and microduplication syndromes are being recognised. This is discussed further in week 3.

Translocations

A translocation describes when a portion of one chromosome is transferred to another chromosome. Translocations can be balanced or unbalanced depending upon whether there is a net gain or loss of genetic material. They are broadly classified into Reciprocal or Robertsonian translocations.

a. Reciprocal translocations arise when any two chromosomes swap non-homologous segments. A carrier of a balanced reciprocal translocation may have offspring with an unbalanced translocation i.e. trisomy of one of the translocated segments and monosomy of the other.

b. Robertsonian translocations describe when two acrocentric chromosomes are “stuck together”. Acrocentric chromosomes are chromosomes where the centromere is very close to the end and include chromosomes 13, 14, 15, 21, 22 and Y.

Inversions

An inversion is when a section of the chromosome has broken away, twisted around 180° (i.e. inverted end to end) and re-inserted into the chromosome. If this section spans the centromere, it is called a pericentric inversion. If the inversion does not include the centromere, it is called a paracentric inversion.

Usually inversions are not associated with any loss or gain of genetic material and so a carrier is asymptomatic (unless a critical gene is disrupted at the breakpoints which is rare). They may only become aware of their carrier status if they have a child with an unbalanced arrangement or they have chromosome investigations for infertility or recurrent miscarriages.

Just for fun - Spot the difference!

Download these images and spot the difference! Can you identify the deleted chromosome region?